Second Cancers in Patients With Locally Advanced Prostate Cancer Randomized to Lifelong Endocrine Treatment With or Without Radical Radiation Therapy: Long-Term Follow-up of the Scandinavian Prostate Cancer Group-7 Trial

Background: Curative radiation therapy (RT) constitutes a cornerstone in prostate cancer (PC) treatment. We present long-term follow-up estimates for second cancer (SC) risk and overall survival (OS) in patients randomized to hormone therapy (ET) alone or combined with 70 Gy prostatic RT in the Scandinavian Prostate Cancer Group-7 (SPCG-7) study. We explored the effect of salvage RT (≥60 Gy to the ET group) and reported causes of death.

Methods and materials: The SPCG-7 study (1996-2002) was a randomized controlled trial that included 875 men with locally advanced nonmetastatic PC. In this analysis, including data from the Norwegian and Swedish Cancer and Cause of Death registries for 651 Norwegian and 209 Swedish study patients, we estimated hazard ratios (HRs) for SC and death, and cumulative incidences of SC.

Results: Median follow-up of the 860 (431 ET and 429) ET + RT patients was 12.2 years for SC risk analysis and 12.6 years for the OS analysis. Eighty-three of the Norwegian ET patients received salvage RT, and median time to salvage RT was 5.9 years. We found 125 and 168 SCs in the ET and ET + RT patients, respectively. With ET alone as reference, ET + RT patients had an HR of 1.19 (95% confidence interval [CI], 0.92-1.54) for all SCs and 2.54 (95% CI, 1.14-5.69) for urinary bladder cancer (UBC). The total number of UBC was 31 (23 in ET + RT; 8 in ET), and the vast majority (85%) were superficial. The HR for SC in salvage RT patients was 0.48 (95% CI, 0.24-0.94). Median OS was 12.8 (95% CI, 11.8-13.8) and 15.3 (95%, CI 14.3-16.4) years in the ET and ET + RT groups, respectively. Compared with ET alone, the risk of death was reduced in ET + RT patients (HR, 0.73; 95% CI, 0.62-0.86) and in ET patients receiving salvage RT (HR, 0.44; 95% CI, 0.30-0.65).

Conclusions: Although the risk of UBC was increased in PC patients who received RT in addition to ET, this disadvantage is outweighed by the OS benefit of RT confirmed in our study. The risk of SC, and especially UBC, should be discussed with patients and be reflected in follow-up programs.